We propose to investigate the possible mechanisms involved in the regulation of the immune response elicited by a single injection of a persisting antigen into rabbits and mice. After a single intravenous injection of aggregated human gamma globulin (AHGG) into rabbits, a cyclic appearance of plaque forming cells (PFC) which apears to be synchronized is observed in the spleen and blood. The properties of the cell types involved in the cyclic appearance of PFC will be investigated. In addition, the nature of the second and third peaks of PFC which occur on days 13 and 21 after antigen injection will be studied. Experiments have been designed to determine if cell division precedes the appearance of the PFC. The effect of sublethal whole body irradiation on the various peaks will also be investigated. The avidity of the antibody produced by the PFC at different times will be determined and compared. A correlation betwen the appearance of PFC and antigen-binding cells will also be made. Since interferon has recently been shown to cause a marked inhibition of the immune response, the kinetics of the appearance of interferon in serum will be compared with the kinetics of the cell cycling. Attempts will be made to establish a similar model (with the same or other antigens) in the mouse. With this model, cell transfer experiments will be used to identify the cell types involved. The possible roles of suppressor T cells and interferon will also be studied. Since newborn rabbits respond to AHGG, the ontogeny of the cyclical appearance of PFC will also be studied.